Background. Acute myeloid leukemia (AML) is an aggressive malignancy of the hematopoietic system. Most patients with newly diagnosed AML are 65 years of age or older. Treatment of this cohort of patients is difficult due to the comorbidity of elderly patients and the genetic characteristics of hemoblastosis, which prevents the achievement of significant progress in treatment, in contrast to younger patients with AML. As domestic and foreign studies have shown, age is an independent universal prognosis factor for AML. In the era of targeted drugs, successful treatment of AML is becoming possible.

Aim. To assess overall survival in elderly patients with AML, tolerability and effectiveness of various treatment regimens in patients with AML ≥65 years.

Materials and methods. This paper presents our own experience in the treatment of elderly patients with AML in the hematology departments of the City Clinical Hospital No. 52. The study included patients over 65 years of age with AML from April 2022 to September 2023. A total of 40 patients were analyzed. To determine the risk factors for death, univariate and multivariate regression analyzes were performed using the logistic regression method. Variables that showed statistical significance on univariate analysis were included in the multivariate analysis. An analysis of 12‑month overall survival was also carried out using the Kaplan–Meier method with the construction of survival curves and calculation of median survival. A comparative analysis of two groups of patients treated with the AZA + EN and LdaraC regimens was carried out.

Results. 63 % (n = 25) are men, 37 % (n = 15) are women. The median age was 75 years; all patients had complicated premorbid background. 53 % (n = 21) of patients were in the age range from 65 to 69 years, 47 % (n = 19) were over 70. Antitumor treatment was received by 88 % (n = 35) of patients. The remaining 5 underwent: best accompanying (n = 2), cytoreductive (early death at this stage) (n = 3) therapy. Complete remission after two cycles of therapy was achieved in 46 % (n = 16) of patients, and in 29 % (n = 10) it was maintained at the time of analysis. Early relapse occurred in 14 % (n = 5). Early mortality was recorded in 9 % (n = 3). Death was reported in 40 % (n = 16) of patients. 20 % (n = 7) of patients were refractory to first-line therapy, of which 36 % (n = 5) were treated with low doses of cytarabine (LdaraC), the rest to a combination of azacitidine (AZA) with venetoclax (EN). The number of relapses among patients on AZA + EN and LdaraC therapy was comparable.

Conclusion. AZA + EN is the first-line treatment of choice in older patients with AML. The possibility of conducting this course in an outpatient setting makes it most convenient for both hematologists and patients. An important aspect in the treatment of AML in elderly patients is improving and maintaining quality of life.

Backround. A progress in Tcell acute lymphoblastic leukemia (TALL) treatment has been achieved in recent years by use a combination of riskadopted chemoradiation therapy, based on highdose (5000 mg/m²) methotrexate. A prerequisite for successful therapy is carefully follow supportive care principles and recommendations, which include blood serum methotrexate concentration monitoring, leucovorin rescue and alkaline solutions use for the best methotrexate elimination and decrease its toxic effects.

Aim. To assess the effectiveness of ALL ICFM 2002 protocol based on highdose methotrexate for Tcell acute lymphoblastic leukemia.

Materials and methods. From 2003 to 2023 in retroprospective study 67 patients with primary diagnosed TALL were enrolled. Median age was 7.4 years (from 0 to 18 years). All the patients were treated according to riskadopted ALL ICFM 2002 protocol. The therapy efficacy was assessed by overall (OS), eventfree (EFS) and relapsefree survival analysis. The survival rates were calculated with statistic program SSS 21.0 by Kaplan–Meier method.

Results. The use of highdose methotrexate for TALL treatment in ALL ICFM 2002 protocol secure high survival rates: 10‑year OS was 82.5 ± 3 %, EFS – 79.3 ± 3 %. Analyzing OS and EFS depending on prognostic risk group we found that standard risk patients had OS and EFS 85.4 ± 6.9 and 78.4 ± 8 %, intermediate – 85.6 ± 6.7 and 82 ± 7.3 % and highrisk – 34.6 ± 18.3 and 20.8 ± 17.1 % respectively (р >0.05).

Conclusion. ALL ICFM 2002 protocol for TALL includes highdose (5000 mg/m²) methotrexate is an effective for standard and intermediate risk patients, but for TALL patients with unfavorable prognostic factors it is necessary a therapy modification by additional cytotoxic and targeted options (nelarabine and daratumumab) inclusion and widening the indications for allogeneic stem cell transplantation.

Background. Thrombopoietin receptor agonists (TORAs), which can imitate the biological effect of thrombopoietin, have shown high efficacy in a number of clinical studies and real clinical practice in patients with resistant primary immune thrombocytopenia (IT). It seems extremely relevant to evaluate the success of using various TORAs in a longterm nonrandomized study and their comparative effectiveness.

Aim. To evaluate the longterm efficacy of TORAs (romiplostim and eltrombopag) in patients with primary IT who are resistant to standard therapy, and to determine the clinical and hematological factors predicting the efficacy of TORAs therapy.

Materials and methods. The study included 456 patients with primary IT (127 (28 %) men and 329 (72 %) women) who were resistant to standard therapy. atients received TORAs therapy at the otkin Hospital. The median age at the start of TORAs therapy was 59 (9–91) years. Romiplostim was received by 339 patients (95 (28 %) men and 244 (72 %) women), eltrombopag – 117 (32 (27 %) men and 85 (73 %) women).

Results. The median duration of TORAs therapy was 78 (1–583) weeks for romiplostim and 59 (1–572) weeks for eltrombopag. uring the TORAs therapy the platelet response was obtained in 89 % (n = 405) of cases in total group of IT patients, in the romiplostim group – in 90 % (n = 306), in the eltrombopag group – in 85 % (n = 99). y the time of data analysis in the total cohort of IT patients, 55 % (n = 253) of patients maintained a sustained platelet response, with a median duration of 159 (2–655) weeks. Among patients receiving romiplostim, these parameters were 59 % (n = 200) and 149 (2–655) weeks, for eltrombopag – 45 % (n = 53) and 240 (24–565) weeks, respectively. The 10‑year overall survival rate with TORAs therapy, regardless of the drug chosen, was 86 %. Negative predictors of achieving a platelet response to romiplostim therapy were identified: ≥2 lines of previous therapy (p = 0.03), a history of splenectomy (p = 0.02). No negative predictors of platelet response to eltrombopag therapy were identified.

Conclusion. The longterm efficacy of 2 drugs of the same therapeutic class (TORAs), romiplostim and eltrombopag, in patients with resistant IT was demonstrated in a direct comparative analysis in a nonrandomized study. Clinical and hematological factors predicting the longterm effectiveness of romiplostim were identified.

Background. L-asparaginase is an integral part of chemotherapy regimens in treatment of patients with acute lymphoblastic leukemia (ALL). However, the use of L-asparaginase is limited due to wide range of adverse reactions. Our research demonstrates the toxicity effects and treatment results in patients with ALL who received native and pegylated (EG) L-asparaginase.

Materials and methods. From 2013 to 2023 in the study 199 patients with newly diagnosed ALL were enrolled. Patients were treated according to the ALL IC-BFM 2009 protocol including L-asparaginase. The average age of patients was 4.6 (1–18) years. B-ALL was diagnosed in 175 (87.9 %) patients, T-ALL in 24 (12.1 %) patients. Native L-asparaginase was used in the therapy of 51 (25.6 %) patients; if allergic reactions occured, 72 (36.2 %) patients received EG asparaginase. In 76 (38.2 %) patients treatment protocol included only EG-asparaginase without native L-asparaginase history.

Results. The most common adverse event was a hypersensitivity reaction – 27.6 % (n = 55), which was more common in the cohort of patients receiving native L-asparaginase. The incidence of hypercoagulation for patients treated with native L-asparaginase was 4 % and 0 % – for EG-asparaginase group. Hypocoagulation, presented as hypofibrinogenemia registered in 13 % of patients received native L-asparaginase and in 35 % for EG-asparaginase group. ancreatitis, complicated ALL treatment were diagnosed in 4 % after native L-asparaginase and 1 % after EG-asparaginase. The best 5‑year survival rates were observed in the group of patients who initially received EG-asparaginase – overall and eventfree survival were 100 and 87.5 (11.7) %, respectively (р >0.05).

Conclusion. Despite the absence of convincing survival benefit in patients with newly diagnosed ALL treated with EG-asparaginase, the toxicity profile was better in contrast to native L-asparaginase.

Classical Hodgkin’s lymphoma (cHL) is a lymphoproliferative disease characterized by the presence of Hodgkin anderezovsky–Reed–Sternberg cells and a tumor microenvironment. Currently, much attention is paid to the microenvironment in cLH. A detailed understanding of the interaction between the tumor and its microenvironment opens up prospects for the cHL diagnosis and treatment. Innovative immunotherapeutic agents such as nivolumab make it possible to control and activate the immune response. Despite the high efficiency of standard protocols in young patients, therapy intensification is associated with organ toxicity and the development of secondary malignant neoplasms. At the same time, in elderly patients, the results of generally accepted antitumor treatment protocols should be considered suboptimal. In the last decade, the treatment of refractory cHL has improved significantly due to the use of immune checkpoint inhibitors.

Taking into account the above, the priority issue in modern clinical hematology is to improve cHL treatment strategies not only in elderly but also in young patients by maintaining a balance between high efficacy and low toxicity. Moreover, the inclusion of nivolumab in first-line therapy is not only pathogenetically justified and effective, but also safe. The article presents data from clinical observations of the successful nivolumab use in combination with chemotherapy in patients with newly diagnosed cHL.

Background. One approach to improving overall and relapsefree survival for patients with acute leukemia is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The probability of relapse after allo-HSCT in acute leukemia patients may be influenced by many factors, including the presence of minimal residual disease (MR) before allo-HSCT. Aim. To evaluate the relationship between MR presence in first complete remission and probability of relapse after allo-HSCT in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Materials and methods. The study included 241 patients: 143 with AML and 98 with ALL (30 patients with Ph-positive leukemia, 22 patients with T-cell ALL and 46 patients with B-cell ALL) who received allo-HSCT at the National Medical Research Center for Hematology from September 2015 to July 2021. The MR analysis was performed using flow cytometry. Statistical analysis was performed using BIM SPSS v. 23 (SA).

Results. Univariate event analysis revealed that in AML patients, poor prognosis was most associated with MRD-positive status before allo-HSCT (hazard ratio (HR) 10.249 (95 % confidence interval (CI) 4.137–25.388); p ˂ .0001). Multivariate analysis included MRD-positive status before allo-HSCT (HR 9.161 (95 % CI 3.513–23.652); p < 001), ELN risk (HR 4.423 (95 % CI 1.764–11.092); p ˂ 0.0034), and transplant source (bone marrow/peripheral stem cells) (HR 3.068 (95 % CI 1.188–7.924); p ˂ 0.0156). Three-year overall and relapse-free survival of AML patients in the first complete remission with MRD-positive status were statistically significantly worse than in patients with MRD-negative status (overall survival 43 % versus 78 %; p = 0.0004; relapse-free – 26 % versus 67 %; p ˂ .0001). In the univariate event analysis, it was found that MRD-positive status before allo-HSCT (HR 4.180 (95 % CI 1.333–13.112); p = 0.0142) was most associated with an unfavorable prognosis in ALL patients. In the multivariate analysis, only the MRD status before allo-HSCT was selected (p = 0.0005). The overall survival of MRD-positive ALL patients, although significantly worse, did not differ statistically significantly from that of MRD-negative patients who received allo-HSCT in the first complete remission (28 % versus 68 %; p = 0.09).

Conclusion. MRD analysis before allo-HSCT helps to identify a group of patients with an extremely high risk of relapse after transplantation, which dictates the need to correct therapeutic tactics regarding the choice of donor, conditioning regimen, immunosuppressive therapy, or early prophylactic antirelapse therapy.

Background. Diffuse large B-cell lymphoma (DLBCL) is a potentially curable biologically heterogeneous lymphatic tumor. Standard R-CHOP therapy shows disappointing results, both immediate and longterm. To improve efficacy without additional toxicity, it is worth considering the possibility of using biologically oriented therapy.

Aim. To evaluate the clinical efficacy and toxicity of the genotypedirected R-CHOP-X in patients with newly diagnosed DLBCL in real clinical practice.

Materials and methods. A single-center prospective interventional clinical study included 30 patients with newly diagnosed DLBCL between September 2023 and September 2024. The median age was 60 (38–78) years. According to the international prognostic index, 23 (77 %) patients were classified as having a high risk of progression. Genotype incidence in the study cohort: MCD – 7 %, N1 – 20 %, BN2 – 7 %, EZB– 16 %, ST2 – 7 %, NOS – 43 %.

Results. 30 patients received personalized genotype-directed therapy. Of these, 21 (70 %) patients completed treatment: the overall response rate was 100 % (complete metabolic response – 100 %). 9 (30 %) patients continue therapy: the overall response rate is 100 %. At 12 months, overall survival and progression-free survival were 100 % (95 % confidence interval 100 %). Hematological toxicity was assessed depending on the number of cycles (n = 144): grade III–I neutropenia was detected in 7 % of cycles, grade III–I anemia and grade III–I thrombocytopenia in 1.4 and 3.5 % of cycles, respectively. Non-hematological toxicity was generally grade ≤I–II.

Conclusion. The results of this clinical trial are promising and provide preliminary evidence for the benefit of personalized genotype-directed antitumor therapy in newly diagnosed DLBCL. This therapeutic strategy demonstrates high clinical efficacy, particularly in the main target group – DLBCL with a high risk of progression with low toxicity. Further randomized studies are needed to confirm the effectiveness and implement the new approach in routine clinical practice.

Background. The T315I mutation in BCR::ABL1 kinase domain determines the resistance of leukemia cells to tyrosine kinase inhibitors (TKIs) – imatinib and secondgeneration TKIs – in patients with chronic myeloid leukemia (CML). The impact of new T315I-targeted approaches on treatment outcomes is being actively studied.

Aim. To evaluate the clinical characteristics and therapy approaches in chronic-phase CML patients with T315I mutation in clinical practice. An additional objective is to evaluate overall survival (OS) by considering the therapy provided.

Materials and methods. The non-interventional retrospective multicenter study included 88 adult patients with chronic-phase CML and the T315I mutation identified between January 2015 and November 2023, with a follow-up period of ≥3 months from 6 hematology clinics in Russia. T315I-targeted therapy refers to TKIs registered in Russia with clinically proven efficacy against the T315I mutation – ponatinib and asciminib, as well as allogeneic hematopoietic stem cell transplantation.

Results. The median time from diagnosis to T315I mutation detection was 47 (6–192) months. Patients with T315I received 1–6 lines of therapy; most often, the T315I mutation was detected after 2–3 lines of therapy. After T315I mutation detection, 68 (77 %) patients received T315I-targeted therapy. The probability of receiving T315I-targeted therapy was 51; 61; 74 and 84 % at 6; 12; 24 and 36 months after T315I mutation detection, respectively, and was statistically significantly higher in patients with a detected mutation in 2018–2019 and 2020–2023 compared to 2015–2017 (p = 0.0256). The time to the first T315I-targeted approach was significantly reduced by year of mutation detection (p = 0.0002); the median time to T315I-targeted therapy over these periods was reduced from 17.8 to 2 months. Allogeneic hematopoietic stem cell transplantation was performed in 22 (25 %) of 88 patients: in 9 (41 %) – as the 1st T315I-targeted therapy; in 13 (59 %) patients, asciminib or ponatinib were used as bridge-therapy before it. Overall survival in the total group (n = 88) was 95; 79 and 68 % at 12; 36 and 60 months, respectively. The OS of patients with identified T315I mutation after 2020 was higher than in 2015–2017 and 2018–2019 periods, but the differences were not statistically significant (p = 0.1625).

Conclusion. Selection of resistant clones with the T315I mutation can occur after any line of 1st–2nd generation TKI therapy. Improved availability of T315I-targeted therapy in Russia has been demonstrated depending on the period of T315I mutation detection. When the time to T315I-targeted therapy was reduced, a trend towards improved OS was observed. The differences in OS estimates identified may be related to selection factors given the retrospective nature of the study. Detailed prospective studies are required to evaluate the efficacy of different T315Idirected therapy protocols.

Background. The leading role in the control of the immune response and peripheral tolerance is played by T-regulatory cells, as well as costimulatory molecules C28 on T-lymphocytes, which are necessary for effective activation. While T-regulatory cells in immune thrombocytopenia (IT) are actively studied in order to find an effective influence on their functions, publications on the study of costimulation processes in this disease are quite rare. Given the pronounced immunosuppressive effect of glucocorticosteroids (GCS) used in the treatment of patients with IT, it seems particularly relevant to study the role of T-regulatory cells and the expression features of costimulatory C28 molecules on T-lymphocytes to expand our understanding of the disease pathogenesis and justify new approaches to treating patients in real clinical practice.

Aim. To evaluate the clinical and prognostic significance of T-regulatory cells and C28 expression on peripheral blood T-lymphocytes in patients with newly diagnosed IT and resistant to GCS therapy.

Materials and methods. The content of T-regulatory cells and C28 expression features on peripheral blood T-lymphocytes were studied by flow cytometry in 18 patients with newly diagnosed IT and 19 patients resistant to GCS therapy. Thirty healthy individuals were examined as a control group.

Results. A significant (p ˂ 0.05) decrease in the content of classical T-regulatory cells (C4⁺C25^+hiC127^–) was revealed both in patients with newly diagnosed IT and in those resistant to GCS, while no significant differences were found in C8⁺C28^– peripheral T-regulatory cells level in patients with IT of both groups compared to healthy individuals. In patients with IT of both groups, a significant increase in the proportion of T-helper (p < 05; p ˂ 01, respectively) and cytotoxic C8⁺ (p ˂ 0.05; p ˂ 0.01, respectively) T-lymphocytes expressing C28 was found compared to normal values. The level of T-helper lymphocytes (C4⁺C28^–) was 2 times higher in the group of patients with resistance to GCS compared to newly diagnosed IT patients, and 3.5 times higher compared to healthy individuals.

Conclusion. T-regulatory cells and expression of C28 costimulatory molecules play an important role in the immunopathogenesis of IT. A significant increase in the content of the C4⁺C28^null lymphocyte population (C4⁺C28^–) in the peripheral blood of IT patients can be a prognostic criterion for GCS resistance, which may require a revision of the treatment strategy.

Background. Data from real-life clinical practice studies provide additional information on the efficacy of new antitumor therapy regimens, including in patients who meet exclusion criteria for clinical trials.

Aim. To evaluate the Isaomex triplet efficacy in multiple myeloma patients in real clinical practice.

Materials and methods. From 2021 to 2024, the retrospective study included 83 double refractory multiple myeloma patients from 26 centers aged 38 to 85 years (median 63), who received the Isaomex triplet. Glomerular filtration rate ˂ 60 mL/min was detected at the time of isatuximabbased triplet initiation in 18 % patients, 2 of whom were on program hemodialysis. The median of previous therapy lines was 2 (1–6). The median time from diagnosis to initiation of isatuximabbased triplet therapy was 47 months (5–203). Survival curves were constructed using the Kaplan–Meier method. Statistical analysis was performed using Statistica 10 program.

Results. Isaomex triplet therapy resulted in overall and renal responses in 76 % and 61 % of cases, respectively. The median progression free survival was 13.5 months. In the group of patients who did not receive daratumumab at previous stages, the median progression free survival was significantly higher and was 28 months vs 8 months (p ˂ 0.05). Threeyear overall survival was 81 %. Discontinuation of isatuximab due to the development of adverse event was recorded in 2 cases (2 %). In the group of patients with bone plasmacytomas (n = 46), Isaomex therapy resulted in an overall response rate of 67 %; 12‑month progression free survival was 48 %, and 1‑year overall survival was 76 %.

Conclusion. The results of the Isaomex triplet use in real clinical practice for the treatment of relapsed multiple myeloma showed data comparable to the ICARIA registration study on the frequency of achieving a response, duration of progression free survival and overall survival. The triplet efficiency was shown in comorbid patients, with advanced stages and those undergoing renal replacement therapy.

Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignant neoplasms, the substrate of which is the clonal proliferation of myelopoiesis progenitor cells. The key AML features are uncontrolled proliferation and arrest of cell differentiation, which leads to specific damage of various organs and systems; in the absence of specific therapy, death occurs quite quickly.

Spontaneous AML remission is considered a rare phenomenon. In 1878, the first mention of AML clinical manifestations regression after acute infectious disease was made, but the remission was short and a relapse soon occurred.

The article presents a literature review and 3 clinical cases, systematizing information on known cases of spontaneous AML remission in children. Attention is focused on various mechanisms that may contribute to spontaneous AML remission in children. These may be either immune-mediated reactions to leukemic cells or the influence of infectious agents, which in some cases activate antitumor immunity. In some cases, a direct correlation is observed between the presence of infectious processes and a decrease of tumor cells number, which emphasizes the importance of further studying the molecular mechanisms of interaction between immune and tumor cells.

There is no evidence of a correlation between age and spontaneous remission. Spontaneous remission, although rare, may be a significant factor to consider when planning a treatment strategy.

Further clinical studies are needed to better understand the spontaneous remission mechanisms in childhood AML. This may lead to improved treatment results and increased chances of a favorable outcome for patients.

Background. Myelodysplastic syndrome is a group of malignant blood diseases with a high risk of transformation into acute myeloid leukemia. One treatment approach is to target immune checkpoints (ICs) that are overexpressed on tumor cells. To develop these drugs, relevant models are needed for highthroughput screening and study of these biologically active substances, since traditionally used models (mouse and patient biomaterials) are difficult to access, financially and laborintensive, and are characterized by poorly reproducible results.

Aim. To develop a model based on a human myeloid cell line with increased expression of L1 and TIM3 to study the activity of ICs inhibitors, the presence of which in the tumor microenvironment in patients with myelodysplastic syndrome and acute myeloid leukemia was associated with a high risk and worse prognosis.

Materials and methods. Initial testing of the L1 and TIM3 basal expression level was carried out on cell lines: TH1, HL60, OCIAML2, OCIAML5, KG1, MonoMac1. Induction of IC expression was carried out using interferon γ. Analysis of marker expression was carried out 24 hours after induction of ICs expression and addition of MK2206 using flow cytometry.

Results. Basal expression of the studied ICs receptors was absent in all of them, except for KG1; TIM3 was present in 88.4 ± 7.1 % of cells, and L1 – in 88 ± 8.5 %. The addition of interferon γ at a concentration of 50 ng/mL to the MonoMac1 culture led to a significant increase in the proportion of TIM3 and L1 expressing cells (53.3 ± 12.2 and 97.3 ± 1.1 % respectively, compared to 0.1 ± 0.1 and 0.1 ± 0.1 % without interferon γ), and for TH1 only L1 expression (87.5 ± 20 %, control 0.1 ± 0.1 %) was observed at the concentration of interferon γ in a medium of 50 ng/mL, while the proportion of cells expressing TIM3 was 6.9 ± 10 % (control 0.1 ± 0.1 %).

Conclusion. The KG1 line, which constantly expresses significant levels of target ICs, as well as TH1 and MonoMac1, which are induced by 50 ng/mL interferon γ, were selected as a model with increased L1 and TIM3 expression based on a human myeloid cell line. The model efficiency was confirmed by the rational response to the IC pathway inhibitor.

Background. Autologous hematopoietic stem cell transplantation remains in demand for patients with hematological malignancies. The pool of hematopoietic stem cells is known to be heterogeneous. e studied various factors associated with previous treatment, patient and disease characteristics, as well as the composition of the C34⁺ pool in peripheral blood (), associated with the number of C34⁺ cells in the first leukocyte concentrate (LC).

Aim. To determine the factors associated with C34⁺ , C34⁺ C143⁺ , C34⁺ C38^– HLA-DR^+/– and C34⁺ C38^+/– HLA-DR^– cells count in the first LC of patients with hematological malignancies.

Materials and methods. Subpopulations of hematopoietic stem cells in the and first LC were studied in 80 patients with hematological malignancies (male to female ratio 1:1, median age 51 years). The control group included 24 healthy donors. Flow cytometry was used to determine the number of C34⁺, C34⁺ C38^– HLA-DR^+/–, C34⁺ C38^+/– HLA-DR^– and C34⁺ C143⁺ cells. Immunophenotyping was performed on samples of patients before mobilization and on the 1st day of leukapheresis, as well as on first LC samples on the 1st day of hematopoietic stem cells collection.

Results. It was shown that the presence of early progenitor cells with C34⁺ C38^– HLA-DR^+/– immunophenotype in the before mobilization is associated with a higher first LC C34⁺ cells number (p = 0.003). In the presence of C34⁺ C38^– HLA-DR^+/– cells in the before mobilization, the median number of C34⁺ cells in the first LC was 2.6 %, and in their absence – 0.71 %. hen using granulocyte colonystimulating factor as monotherapy, the C34⁺ C143⁺ cells number in the first LC was significantly lower than when using chemotherapy and granulocyte colonystimulating factor (p = 0.03). However, the majority (9 of 16) of patients in the granulocyte colonystimulating factor monotherapy group had renal failure before mobilization. No factors associated with the number of C34⁺ C38^– HLA-DR^+/– cells in the first LC were found. In patients >60 years old, the number of C34⁺ C38^+/– HLA-DR^– cells in the first LC was lower than in patients ˂ 60 years old, the number of C34⁺ C38^+/– HLA-DR^– cells in the first LC was lower than in patients ˂ 60 years old (p = 0.043). In patients with infectious complications during hematopoietic stem cell mobilization, the number of C34⁺ C38^+/– HLA-DR^– cells in the first LC was lower than in patients without them (p = 0.019).

Conclusion. The first LC number of C34⁺ cells is associated with number of C34⁺ C38^– HLA-DR^+/– cells, i. e. cells of the early differentiation stage with a high proliferation potential. A relationship was established between C34⁺ C143⁺ cells number before mobilization and first LC C34⁺ cells count: in the paired model – within the borderline values (p = 0.05), and in the multifactorial covariance model – with high significance (p = 0.0033). It has been proven that with increasing patient age and in the presence of infectious complications, the number of longterm repopulating C34⁺ C38^+/– HLA-DR^– cells decreases.

Background. Somatic mutations in chronic myeloid leukemia (CML) patients are considered as possible factors for the failure of tyrosine kinase inhibitor (TKI) therapy, and the study of their characteristics is of interest.

Aim. To evaluate the genetic profile of blood cells in CML patients using nextgeneration sequencing.

Materials and methods. Retrospective study was conducted in two groups of patients: group 1 with TKI therapy failure (n = 29) and group 2 with optimal response to TKI therapy (n = 29). The target panel for nextgeneration sequencing included 19 genes: ASXL1, DNMT3A, FLT3, IDH1, IDH2, NPM1, RUNX1, SF3B1, SRSF2, TET2, TP53, U2AF2, KIT, WT1, CEBPA, ZRSR2, JAK2, GATA2, ABL1. In order to assess clonal evolution, additional samples were examined at a retrospective point in time closest to the primary CML diagnosis.

Results. In group 1, mutations in 8 genes (including ABL1) were identified in 19/29 (66 %) patients. Excluding ABL1, mutations were identified in 15 (52 %) patients. In 9 (31 %) patients, >1 mutation (2 to 4) was detected. Frequency of genes mutations in group 1: ABL1 in 11 (38 %) patients, ASXL1 in 9 (31 %) patients, DNMT3A in 3 (10 %) patients, RUNX1, CEBPA in 2 patients (7 %), WT1, NPM1, TET2 in 1 patient (3.5 %). In 7 (24 %) patients there was a combination of mutations in ABL1 gene and in another gene; the most frequent combination of mutations in genes: ABL1 + ASXL1 – in 4 patients (14 %). The dynamics of mutant clones in group 1 was evaluated in 21/29 (72 %) patients. In 10/21 (48 %) patients somatic mutations in genes appeared during CML treatment, in 14/21 (67 %) patients previously detected mutations persisted, in 1 (5 %) the mutation disappeared. In group 2, somatic mutations were detected in 2/29 (7 %) patients: in DNMT3A (ariant Allele Frequency (AF) 5 %) and TP53 (AF 9 %) genes – these mutations were not detected at the diagnosis of CML. In one patient ASXL1 mutation (AF 5 %) was detected only at diagnosis, and was not detected subsequently with optimal response to therapy.

Conclusion. The presence of somatic gene mutations is associated with a resistant CML course: somatic mutations in genes other than ABL1 were more common in CML patients with TKI therapy failure than in those with optimal response: 52 % vs. 7 % (p ≤0.05). Mutations in ASXL1 (31 %) and DNMT3A (10 %) were the most frequently detected. The frequency of ABL1 and ASXL1 mutations combination amounted to 14 %. uring followup, somatic mutations predominantly persisted or appeared over time in CML patients with TKI therapy resistance.

Background. Detection of a somatic mutation in the Janus kinase 2 (JAK2) gene, along with mutations in the CALR and MPL genes, is one of the main criteria for diagnosing Ph-negative myeloproliferative neoplasms (MPN). At the same time, the JAK2 V617F mutation is often associated with agedependent clonal hematopoiesis of undetermined potential (CHIP). As a rule, the indicator reflecting the number of blood cells transformed by mutation – the mutant allelic burden (MAB) of JAK2 V617F in CHIP does not exceed 1–2 %, however, there is no clear boundary between the level of this indicator separating CHIP and MPN. The previously described “JAK2 paradox”, according to which JAK2 V617F positive CHIP predominates in men, and for women this mutation is more associated with MPN, suggests a different attitude to the diagnostic value of MAB between men and women. A separate issue concerns the detection of low MAB levels in combination with other MPN driver mutations.

Aim. To analyze the database of JAK2 V617F mutation allelic burden quantitative assessment results and to identify CALR and MPL genes driver mutations in patients depending on their age and gender.

Materials and methods. Data from records on the age and gender of 6210 patients (3061 men and 3149 women) were analyzed, in whom the JAK2 gene V617F somatic mutation in a quantitative format and MPL and CALR genes mutations were simultaneously determined. Of these, mutations were identified in 1226 women and 826 men with symptoms of MPN. Statistical analysis was performed using Excel spreadsheets and Statistica 10 package.

The results. The data obtained indicate that in women, compared to men, the frequency of the V617F mutation is higher in all age ranges. omen are also more likely to have mutations in the CALR and MPL genes. The gender and age dependence of identifying quantitative values of MAB JAK2 V617F differ significantly in the range of >1 and ˂ 1%. Also noteworthy is the fact of high detection (up to 17–27 %) of additional combined mutations in the CALR and MPL genes in patients with low MAB JAK2 V617F values.

Conclusion. The data support the gender “JAK2 paradox”, which suggests differential interpretation of test results in men and women. To more clearly assess the characteristics of the diagnostic value of MAN JAK2 V617F low levels and its dependence on the gender and age of patients, controlled multicenter clinical studies using standardized diagnostic test systems are needed.

The article presents a review of new data on blast cells metabolism and its regulatory mechanisms in acute myeloid leukemia. Particular attention is given to the role of reactive oxygen species in the regulation of signaling pathways and metabolic processes, as well as their influence on the aggressiveness and resistance to chemotherapeutic agents in acute myeloid leukemia. Elevated levels of reactive oxygen species are associated with altered activity of enzymes and proteins involved in cell proliferation and survival. The article also discusses data on the iron role in the formation of malignancy in acute myeloid leukemia.

Background. Patients with acute myeloid leukemia (AML) are predisposed to infectious complications (IC). Single nucleotide polymorphisms in genes can affect the function and/or expression of the proteins they encode. Since the functioning of the innate immune system is under genetic control, identifying polymorphic variants that reduce the effectiveness of the immune response is a promising method for identifying patients at high risk of severe infections.

Aim. To evaluate the relationship between presence of single nucleotide polymorphisms TLR3 C1234G and IL4 C589T with IC frequency in AML patients.

Materials and methods. TLR3 C1234G and IL4 C589T polymorphisms were genotyped in 93 patients with AML, of which 77 (82.80 %) – de novo AML, 16 (17.20 %) – AML with previous myelodysplastic syndrome. Patients received 263 chemotherapy courses. Median age was 58 (Q1–Q3: 38–66) years, 50 (53.76 %) were men, 43 (46.24 %) were women. Sepsis and pneumonia were considered severe IC. Allele-specific polymerase chain reaction with detection of amplification products in a 3 % agarose gel was used to genotype single nucleotide polymorphisms in immune response genes.

Results. Severe IC were developed in 57 (21.67 %) chemotherapy courses. It was found that in patients with the TLR3 1234GG genotype, compared with carriers of the TLR31234CC genotype, the frequency of severe IC is 4.8 times lower (odds ratio 0.21; p = 0.022). Severe IC occurred 2.3 times more often in heterozygous carriers of the IL4 C589T polymorphism than in homozygous carriers of the C allele (odds ratio 2.29; p = 0.025). In multivariate analysis, taking into account age, gender and severity of neutropenia, the TLR31234GG and IL4 589CT genotypes variants remained independent predictors of IC.

Conclusion. The TLR3 1234CC and IL4589CT genotypes are associated with the risk of severe IC in AML patients.

Malnutrition is a significant problem for patients with hematological neoplasms and solid tumors, serving as a negative prognostic and predictive factor that reduces the effectiveness of anticancer therapy and worsens survival outcomes.

The article discusses the role of nutritional support in improving treatment outcomes, reducing complications, and enhancing the quality of life for cancer patients. It reviews current clinical guidelines for the implementation of nutritional support in oncology and oncohematology, underscoring the necessity of early intervention and continuous monitoring to prevent and address nutritional deficiencies. Various methods of nutritional support, including oral, enteral, and parenteral nutrition, are also discussed, with an emphasis on the importance of a personalized approach to meet the individual needs of patients.